RT Journal Article
SR Electronic
T1 The Expression and Functional Role of Nicotinic Acetylcholine Receptors in Rat Adipocytes
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 52
OP 58
DO 10.1124/jpet.103.065037
VO 310
IS 1
A1 Run-Hua Liu
A1 Masanari Mizuta
A1 Shigeru Matsukura
YR 2004
UL http://jpet.aspetjournals.org/content/310/1/52.abstract
AB To clarify whether nicotine has a direct effect on the function of adipocytes, we evaluated nicotinic acetylcholine receptor (nAChR) expression in adipocytes by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry and the direct effects of nicotine on the production of adipocytokines by enzyme-linked immunosorbent assay and Western blot analysis. Receptor binding assays were performed using [3H]nicotine. RT-PCR studies revealed that α1–7, 9, 10, β1–4, δ, and ϵ subunit mRNAs are expressed in adipocytes. Immunocytochemical experiments also suggested the presence of α7 and β2 subunits. The receptor binding assay revealed a binding site for nicotine (Kd = 39.2 × 10-9 M) on adipocytes. Adipocytes incubated with nicotine for 12 and 36 h released tumor necrosis factor-α (TNF-α), adiponectin, and free fatty acid (FFA) into the medium in a dose-dependent manner with increasing nicotine concentration from 6 × 10-8 to 6 × 10-4 M. However, TNF-α protein levels in adipocytes incubated for 12 and 36 h decreased in a dose-dependent manner with increasing nicotine concentration from 6 × 10-8 to 6 × 10-4 M. These results show that adipocytes have functional nAChRs and suggest that nicotine reduces TNF-α protein production in adipocytes through the activation of nAChRs. Nicotine may temporarily lower insulin sensitivity by stimulating the secretion of TNF-α and FFA, whereas long-term direct stimulation of nAChRs by nicotine in addition to autonomic nervous system stimulation may contribute to better insulin sensitivity in vivo through a modulated secretion of adipocytokines. The American Society for Pharmacology and Experimental Therapeutics